Fig. 2.
Early stages of thyroid tumor development following spontaneous BrafCA activation in TgCreERT2;BrafCA/+ mutant mice. (A) Histogram showing H&E staining of heterotypic follicular abnormalities of the thyroid from a mouse aged 3 months (mo). The boxed area is shown magnified in A′. Asterisks indicate follicles with translucent interior, i.e. lack of colloid. (B-D) Quantitative assessment of changes within the thyroid in response to mutant BRAF kinase inhibition. Dietary pellets with PLX4720 were supplied daily at 417 ppm from 4 weeks onwards and until mice were killed aged 3 months; data were obtained from serial sections. The number of neoplastic follicles in untreated mutants (individual data) is plotted in B. Inhibition of thyroid enlargement (individual data; mean±s.d.; *P<0.005) is plotted in C. Heterogeneous drug response in neoplastic lesions. The mean±s.d. (*P<0.005) of (n): wt (5); untreated mutants (7), drug-treated mutants (9) is plotted in D. (E) Representative image of the thyroid from a mutant mouse aged 6 months, immunostained for thyroglobulin (TG), showing loss of TG in neoplastic lesions. Boxed areas in E are shown magnified in E′ and E′′. Asterisks in E′ and E′′ indicate follicles with altered shape and retained TG in the lumen. L, left lobe; R, right lobe. nf, normal follicle; hf, hyperplastic follicle; gf, giant follicle; arrows indicate hyperplastic epithelium; arrowheads indicate flat epithelium; wt, control wild-type (non-mutant) mice. Scale bars: 500 µm.